RU2006112343A

RU2006112343A - HETEROCYCLIC COMPOUNDS AND METHODS FOR PRODUCING AND USING THEM

Info

Publication number: RU2006112343A
Application number: RU2006112343/04A
Authority: RU
Inventors: Йелесварапу Коутсвар РАО (IN); Йелесварапу Коутсвар РАО; Маноджит ПАЛ (IN); Маноджит ПАЛ; Ведула Манохар ШАРМА (IN); Ведула Манохар ШАРМА; Акелла ВЕНКАТЕСВАРЛУ (IN); Акелла Венкатесварлу; Рэм Пилларисетти (Us); Рэм Пилларисетти
Original assignee: Редди Юс Терапеутикс, Инк. (Us); Редди Юс Терапеутикс, Инк.
Priority date: 2003-10-28
Filing date: 2004-10-28
Publication date: 2007-12-10
Also published as: WO2005042712A2; AU2004286277A1; IL174249A0; WO2005042712A3; KR20070026306A; JP2008074858A; JP2007509966A; NO20061292L; EP1678157A4; CA2540460A1; EP1678157A2

Claims

1. The compound of General formula (I)

,

its tautomeric forms, its stereoisomers, its polymorphs, its pharmaceutically acceptable salts or its pharmaceutically acceptable solvates,

Where

denotes

one)

; or

2)

;

where L is

,

or - (CH ₂ ) _t -;

where Q is

or

;

where R ¹ , R ² and R ³ independently represent hydrogen, hydroxyl group, halogen, nitro group, carboxy group, carbamoyl group, optionally substituted amino group, alkyl group, cycloalkyl group, alkoxy group, cycloalkoxy group, alkenyl group, cycloalkenyl group, alkoxyalkenyl group, alkoxyalkyl group cycloalkenyloxy group, acyl group, acyloxy group, aryl group, aryloxy group, aroyl group, aryloxy group, aralkyl group, aralkoxy group, heterocyclyl group, heteroaryl group pu, a heteroaralkyl group, a heteroaryloxy geteroaralkoksigruppu, an alkoxycarbonyl group, an aryloxycarbonyl group, a heteroarylcarbonyl group, an alkylsulfonyl group, an arylsulfonyl group, a heteroarylsulfonyl group, aralkilsulfinilnuyu group, an alkylsulfinyl group, an arylsulfinyl group, geteroarilsulfinilnuyu group aralkilsulfinilnuyu group, an alkylthio group, an arylthio group, hetero, aralkylthio, an aryloxyalkyl group, a carboxylic acid or a derivative thereof, or sulfonic acid or its derivative, wherein any two of R ¹ , R ² and R ³ in combination optionally form a 5-membered or 6-membered saturated cyclic ring containing 1-3 heterotomes, where heteroatoms are O, S or N;

where R ⁴ denotes hydrogen, a hydroxyl group, a halogen, a nitro group, a carboxy group, a carbamoyl group, an optionally substituted amino group, an alkyl group, a cycloalkyl group, an alkoxy group, a cycloalkoxy group, an alkenyl group, a cycloalkenyl group, an alkoxyalkyl group, an alkenyloxy group, cycloalkenyl group, cycloalkenyl group, cycloalkyl group, cycloalkyl group, cycloalkyl group , aryl group, aryloxy group, aroyl group, aryloxy group, aralkyl group, aralkenyl group, aralkynyl group, aralkoxy group, heterocyclyl Rupp, heterocyclenyl group, a heteroaryl group, a heteroaralkyl group, a heteroaryloxy geteroaralkoksigruppu, an alkoxycarbonyl group, an aryloxycarbonyl group, an aralkoxycarbonyl group, a heteroarylcarbonyl group, an alkylsulfonyl group, an arylsulfonyl group, a heteroarylsulfonyl group, an alkylsulfinyl group, an arylsulfinyl group, aralkilsulfinilnuyu group geteroarilsulfinilnuyu group aralkilsulfinilnuyu group , alkylthio group, arylthio group, heteroarylthio group, ar an alkylthio group, an aryloxyalkyl group, an aralkoxyalkyl group, a fused heteroarylcycloalkyl group, a fused heteroarylcycloalkenyl group, a fused heteroarylheterocyclenyl group, a carboxylic acid or its derivative or sulfonic acid or its derivative;

where A, B, D and J independently represent O, S, H,> CH or - (CH ₂ ) _n -;

where "-" denotes an optional chemical bond;

where E is O, S or —NR;

where K is N, C or CH;

where Y and Z are independently O, —NR, - (CH ₂ ) _u - or S (= O) _u ;

where G is - (CH ₂ ) _s -, - (CH ₂ ) _s -CH = CH- (CH ₂ ) _s -, or - (CH ₂ ) _s -C = C- (CH ₂ ) _s -;

where X, X ₁ , X ₂ , X ₃ and X ₄ independently represent O, S or -NR;

where F is O, S or —NR;

where Y ¹ and Y ² independently represent O or S;

where n, w, u independently denote an integer selected from 0-2;

where p, t, m, s, v independently represent an integer selected from 0-5;

where R and R ⁵ independently represent hydrogen, potassium, sodium, hydroxyl group, halogen, nitro group, optionally substituted amino group, alkyl group, alkoxy group, alkenyl group, alkoxyalkyl group, cycloalkenyloxy group, acyl group, aryl group, aralkyl group, heteroaryl group or a group; and

where "Ar" refers to substituted or unsubstituted phenyl or a substituted or unsubstituted naphthyl group.

2. The compound according to claim 1, where any of R ¹ , R ² , R ³ and R ^{4 is} independently substituted by hydrogen, halogen, nitro group, amino group, mono - or disubstituted amino group, hydroxyl group, alkoxy group, carboxy group, cyano group, oxo group ( O =), thio group (S =), alkyl group, cycloalkyl group, alkoxy group, haloalkoxy group, cycloalkyl group, aryl group, benzyloxy group, acyl group, acyloxy group, aroyl group, alkoxycarbonyl group, aryloxycarbonyl group, heteroaryl gro drink, a heterocyclyl group, an aralkyl group, an alkylsulfonyl group, an alkylsulfinyl group, an arylsulfonyl group, an arylsulfinyl group, an alkylthio group, an arylthio group or a heterocyclic, hetero, hetero, hetero, hetero, hetero, hetero, hetero, hetero, hetero the group denotes an optionally substituted morpholinyl group, a thiomorpholinyl group or piperazini and a substituent on the heterocyclic group is a halogen, nitro group, amino group, alkyl group, alkoxy group or aryl group.

3. The compound of General formula (II)

where R ¹ , R ² and R ³ independently represent hydrogen, hydroxyl group, halogen, nitro group, carboxy group, carbamoyl group, optionally substituted amino group, alkyl group, cycloalkyl group, alkoxy group, cycloalkoxy group, alkenyl group, cycloalkenyl group, alkoxyalkenyl group, alkoxyalkyl group cycloalkenyloxy group, acyl group, acyloxy group, aryl group, aryloxy group, aroyl group, aryloxy group, aralkyl group, aralkoxy group, heterocyclyl group, heteroaryl group pu, a heteroaralkyl group, a heteroaryloxy geteroaralkoksigruppu, an alkoxycarbonyl group, an aryloxycarbonyl group, a heteroarylcarbonyl group, an alkylsulfonyl group, an arylsulfonyl group, a heteroarylsulfonyl group, aralkilsulfinilnuyu group, an alkylsulfinyl group, an arylsulfinyl group, geteroarilsulfinilnuyu group aralkilsulfinilnuyu group, an alkylthio group, an arylthio group, hetero, aralkylthio, an aryloxyalkyl group, a carboxylic acid or a derivative thereof, or sulfonic acid or a derivative thereof, wherein any two of R ¹ , R ² and R ³ in combination optionally form a 5-membered or 6-membered saturated ring ring containing 1-3 heteroatoms, where the heteroatoms are O, S or N;

where R ⁴ is hydrogen, a hydroxyl group, a halogen, a nitro group, a carboxy group, a carbamoyl group, an optionally substituted amino group, an alkyl group, a cycloalkyl group, an alkoxy group, a cycloalkoxy group, an alkenyl group, a cycloalkenyl group, an alkoxyalkyloxy group, an alkenyloxy group aryl group, aryloxy group, aroyl group, aryloxy group, aralkyl group, aralkenyl group, aralkynyl group, aralkoxy group, heterocyclyl g Rupp, heterocyclenyl group, a heteroaryl group, a heteroaralkyl group, a heteroaryloxy geteroaralkoksigruppu, an alkoxycarbonyl group, an aryloxycarbonyl group, an aralkoxycarbonyl group, a heteroarylcarbonyl group, an alkylsulfonyl group, an arylsulfonyl group, a heteroarylsulfonyl group, an alkylsulfinyl group, an arylsulfinyl group, aralkilsulfinilnuyu group geteroarilsulfinilnuyu group aralkilsulfinilnuyu group , alkylthio group, arylthio group, heteroarylthio group, ar lkiltiogruppu, aryloxyalkyl group aralkoksialkilnuyu group fused geteroariltsikloalkilnuyu group fused geteroariltsikloalkenilnuyu group fused geteroarilgeterotsiklenilnuyu group, a carboxylic acid or a derivative thereof, or sulfonic acid or a derivative thereof;

where A, B, D and J independently represent O, S, H,> CH or - (CH ₂ ) _n -;

where "-" denotes an optional chemical bond;

where E is O, S or —NR;

where Y and Z are independently O, —NR, - (CH ₂ ) _u - or S (= O) _u ;

where X is O, S or —NR;

where F is O, S or —NR;

where Y ¹ and Y ² independently represent O or S;

where n and u independently represent an integer selected from 0-2;

where s is an integer selected from 0-5;

4. The compound according to claim 3, where any of R ¹ , R ² , R ³ and R ^{4 is} independently substituted by hydrogen, halogen, nitro group, amino group, mono - or disubstituted amino group, hydroxyl group, alkoxy group, carboxy group, cyano group, oxo group ( O =), thio group (S =), alkyl group, cycloalkyl group, alkoxy group, haloalkoxy group, cycloalkyl group, aryl group, benzyloxy group, acyl group, acyloxy group, aroyl group, alkoxycarbonyl group, aryloxycarbonyl group, heteroaryl gro drink, a heterocyclyl group, an aralkyl group, an alkylsulfonyl group, an alkylsulfinyl group, an arylsulfonyl group, an arylsulfinyl group, an alkylthio group, an arylthio group or a heterocyclic, hetero, hetero, hetero, hetero, hetero, hetero, hetero, hetero, hetero the group denotes an optionally substituted morpholinyl group, a thiomorpholinyl group or piperazini and a substituent on the heterocyclic group is a halogen, a nitro group, an amino group, an alkyl group, an alkoxy group or an aryl group.

5. The compound of General formula (III)

,

where R ¹ , R ² and R ³ independently represent hydrogen, hydroxyl group, halogen, nitro group, carboxy group, carbamoyl group, optionally substituted amino group, alkyl group, cycloalkyl group, alkoxy group, cycloalkoxy group, alkenyl group, cycloalkenyl group, alkoxyalkenyl group, alkoxyalkyl group cycloalkenyloxy group, acyl group, acyloxy group, aryl group, aryloxy group, aroyl group, aryloxy group, aralkyl group, aralkoxy group, heterocyclyl group, heteroaryl group pu, a heteroaralkyl group, a heteroaryloxy, heteroaralkoxy group, an alkoxycarbonyl group, an aryloxycarbonyl group, a heteroarylcarbonyl group, an alkylsulfonyl group, an arylsulfonyl group, a heteroarylsulfonyl group, aralkilsulfinilnuyu group, an alkylsulfinyl group, an arylsulfinyl group, geteroarilsulfinilnuyu group aralkilsulfinilnuyu group, an alkylthio group, an arylthio group, hetero, aralkylthio , an aryloxyalkyl group, a carboxylic acid or a derivative thereof, or sulfonic acid or its derivative, where any two of R ¹ , R ² and R ³ in combination optionally form a 5-membered or 6-membered saturated cyclic ring containing 1-3 heteroatoms, where the heteroatoms are O, S or N;

where "-" denotes an optional chemical bond;

where E is O, S or —NR;

where Z is O, —NR, - (CH ₂ ) _u - or S (= O) _u ;

where u is an integer selected from 0-2;

where s is an integer selected from 0-5;

where R 'and R "independently represent hydrogen, halogen, nitro group, amino group, mono - or disubstituted amino group, hydroxyl group, alkoxy group, carboxy group, cyano group, oxo group (O =), thio group (S =), alkyl group, cycloalkyl group, alkoxy group , haloalkoxy group, cycloalkyl group, aryl group, benzyloxy group, acyl group, acyloxy group, aroyl group, alkoxycarbonyl group, aryloxycarbonyl group, heteroaryl group, heterocyclyl group, aralkyl group, alkylsulfonyl group uppu, an alkylsulfinyl group, an arylsulfonyl group, an arylsulfinyl group, an alkylthio group, an arylthio group, hetero, aralkylthio or geterotsiklilsulfonilnuyu group.

6. The compound according to claim 5, where any of R ¹ , R ² , R ³ and R ^{4 is} independently substituted by hydrogen, halogen, nitro group, amino group, mono - or disubstituted amino group, hydroxyl group, alkoxy group, carboxy group, cyano group, oxo group (O =), thio group (S =), alkyl group, cycloalkyl group, alkoxy group, haloalkoxy group, cycloalkyl group, aryl group, benzyloxy group, acyl group, acyloxy group, aroyl group, alkoxycarbonyl group, aryloxycarbonyl group, heteroaryl group, an alkyl group, an aralkyl group, an alkylsulfonyl group, an alkylsulfonyl group, an arylsulfonyl group, an arylsulfinyl group, an alkylthio group, an arylthio group, a heteroarylthio group, an aralkylthio group or a heterocyclyl sulfonyl group, an optionally substituted heteroalkyl, hydroxy, hetero, hydroxy, optionally substituted morpholinyl group, thiomorpholinyl group or piperazinyl group wherein the substituent on the heterocyclic group is a halogen, nitro group, amino group, alkyl group, alkoxy group or aryl group.

7. The compound according to claim 5, where one or both of R 'and R "are independently substituted by a halogen, hydroxyl group, nitro group, amino group or alkyloxy group.

8. The compound according to claim 5, where one or both of R 'and R "are independently substituted by a heterocyclyl group, including a morpholinyl group, thiomorpholine or piperazine.

9. The compound of formula (III) according to claim 5, where the compound is a

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

; or

.

10. The compound of General formula (IV)

,

wherein R ¹ and R ² are independently hydrogen, a hydroxyl group, a halogen, a nitro group, a carboxy group, a carbamoyl group, an optionally substituted amino group, an alkyl group, cycloalkyl group, alkoxy group, cycloalkoxy group, an alkenyl group, a cycloalkenyl group, an alkoxyalkyl group, an alkenyloxy group tsikloalkeniloksigruppu, acyl group, acyloxy group, aryl group, aryloxy group, aroyl group, aryloxy group, aralkyl group, aralkoxy group, heterocyclyl group, heteroaryl group, heteroaralkyl group, a heteroaryloxy geteroaralkoksigruppu, an alkoxycarbonyl group, an aryloxycarbonyl group, a heteroarylcarbonyl group, an alkylsulfonyl group, an arylsulfonyl group, a heteroarylsulfonyl group, aralkilsulfinilnuyu group, an alkylsulfinyl group, an arylsulfinyl group, geteroarilsulfinilnuyu group aralkilsulfinilnuyu group, an alkylthio group, an arylthio group, hetero, aralkylthio group, aryloxyalkyl group , carboxylic acid or its derivative or sul fphonic acid or its derivative, wherein any two of R ¹ , R ² and R ³ in combination optionally form a 5-membered or 6-membered saturated ring ring containing 1-3 heteroatoms, where the heteroatoms are O, S or N;

where D and J independently represent O, S, N,> CH or CH ₂ ;

where "-" denotes an optional chemical bond;

where E is O, S or —NR;

where K is N, C or CH;

where Z is O, —NR, - (CH ₂ ) _u - or S (= O) _u ;

where X is O, S or —NR;

where F is O, S or —NR;

where Y ¹ and Y ² independently represent O or S;

where u is an integer selected from 0-2;

where s is an integer selected from 0-5;

11. The compound of claim 10, where any of R ¹ , R ² , R ³ and R ^{4 is} independently substituted by hydrogen, halogen, nitro group, amino group, mono - or disubstituted amino group, hydroxyl group, alkoxy group, carboxy group, cyano group, oxo group (O =), thio group (S =), alkyl group, cycloalkyl group, alkoxy group, haloalkoxy group, cycloalkyl group, aryl group, benzyloxy group, acyl group, acyloxy group, aroyl group, alkoxycarbonyl group, aryloxycarbonyl group, heteroaryl group, a cyclic group, an aralkyl group, an alkylsulfonyl group, an alkylsulfinyl group, an arylsulfonyl group, an arylsulfinyl group, an alkylthio group, an arylthio group, a heteroarylthio group, an aralkylthio group or a heterocyclylsulfonyl group, an optionally substituted heteroalkyl, heteroalkyl, hydroxy, optionally substituted morpholinyl group, thiomorpholinyl group or piperazinyl group where the substituent on the heterocyclic group is a halogen, a nitro group, an amino group, an alkyl group, an alkoxy group or an aryl group.

12. The compound of formula (IV) according to claim 10, where the compound is a

;

;

;

;

;

;

;

;

; or

.

13. The compound of General formula (V)

,

where R ¹ , R ² and R ³ independently represent hydrogen, hydroxyl group, halogen, nitro group, carboxy group, carbamoyl group, optionally substituted amino group, alkyl group, cycloalkyl group, alkoxy group, cycloalkoxy group, alkenyl group, cycloalkenyl group, alkoxyalkenyl group, alkoxyalkyl group cycloalkenyloxy group, acyl group, acyloxy group, aryl group, aryloxy group, aroyl group, aryloxy group, aralkyl group, aralkoxy group, heterocyclyl group, heteroaryl group pu, a heteroaralkyl group, a heteroaryloxy geteroaralkoksigruppu, an alkoxycarbonyl group, an aryloxycarbonyl group, a heteroarylcarbonyl group, an alkylsulfonyl group, an arylsulfonyl group, a heteroarylsulfonyl group, aralkilsulfinilnuyu group, an alkylsulfinyl group, an arylsulfinyl group, geteroarilsulfinilnuyu group aralkilsulfinilnuyu group, an alkylthio group, an arylthio group, hetero, aralkylthio, an aryloxyalkyl group, a carboxylic acid or a derivative thereof, or sulfonic acid or its derivative, wherein any two of R ¹ , R ² and R ³ in combination optionally form a 5-membered or 6-membered saturated cyclic ring containing 1-3 heterotomes, where the heteroatoms are O, S or N;

where R ⁴ represents hydrogen, a hydroxyl group, a halogen, a nitro group, a carboxy group, a carbamoyl group, an optionally substituted amino group, an alkyl group, a cycloalkyl group, an alkoxy group, a cycloalkoxy group, an alkenyl group, a cycloalkenyl group, an alkoxyalkyl group, alkenyloxy group, alkenyloxy group, alkenyloxy group, , aryl group, aryloxy group, aroyl group, aryloxy group, aralkyl group, aralkenyl group, aralkynyl group, aralkoxy group, heterocyclyl Rupp, heterocyclenyl group, a heteroaryl group, a heteroaralkyl group, a heteroaryloxy geteroaralkoksigruppu, an alkoxycarbonyl group, an aryloxycarbonyl group, an aralkoxycarbonyl group, a heteroarylcarbonyl group, an alkylsulfonyl group, an arylsulfonyl group, a heteroarylsulfonyl group, an alkylsulfinyl group, an arylsulfinyl group, aralkilsulfinilnuyu group geteroarilsulfinilnuyu group aralkilsulfinilnuyu group , alkylthio group, arylthio group, heteroarylthio group, ar an alkylthio group, an aryloxyalkyl group, an aralkoxyalkyl group, a fused heteroarylcycloalkyl group, a fused heteroarylcycloalkenyl group, a fused heteroarylheterocyclenyl group, a carboxylic acid or its derivative or sulfonic acid or its derivative;

where A, B, D and J independently represent O, S, N,> CH or - (CH ₂ ) _n -;

where E is O, S or —NR;

where K is N, C or CH;

where L is

,

or (CH ₂ ) _t -;

where Y and Z are independently O, —NR, - (CH ₂ ) _u - or S (= O) _u ;

where X ₁ , X ₂ , X ₃ and X _{4 are} independently O, S or —NR;

where X is O, S or —NR;

where n and w independently denote an integer selected from 0-2;

where p, t and v independently represent an integer selected from 0-5;

where R is hydrogen, potassium, sodium, hydroxyl group, halogen, nitro group, optionally substituted amino group, alkyl group, alkoxy group, alkenyl group, alkoxyalkyl group, cycloalkenyloxy group, acyl group, aryl group, aralkyl group, heterocyclyl group or heteroaryl; and

14. The compound according to item 13, where any of R ¹ , R ² , R ³ and R is independently substituted by hydrogen, halogen, nitro group, amino group, mono - or disubstituted amino group, hydroxyl group, alkoxy group, carboxy group, cyano group, oxo group (O = ), thio group (S =), alkyl group, cycloalkyl group, alkoxy group, haloalkoxy group, cycloalkyl group, aryl group, benzyloxy group, acyl group, acyloxy group, aroyl group, alkoxycarbonyl group, aryloxycarbonyl group, heteroaryl group, an alkyl group, an aralkyl group, an alkylsulfonyl group, an alkylsulfonyl group, an arylsulfonyl group, an arylsulfinyl group, an alkylthio group, an arylthio group, a heteroarylthio group, an aralkylthio group or a heterocyclylsulfonyl group, optionally substituted with a halo group, an alkyl group, an hydroxy group optionally substituted morpholinyl group, thiomorpholinyl group or piperazinyl group where the substituent on the heterocyclic group is a halogen, a nitro group, an amino group, an alkyl group, an alkoxy group or an aryl group.

15. The compound of formula (V) according to item 13, where the compound is a

;

;

;

;

;

;

;

;

;

;

;

;

;

;

;

.

16. A method of treating or preventing a disease mediated by an inflammatory response or proliferation of smooth muscle cells in a human or animal, comprising administering to a human or animal a composition comprising a therapeutically or prophylactically effective amount of a compound according to claim 1.

17. The method according to clause 16, where the inflammatory reaction includes a diabetic vascular complication, where the diabetic vascular complication includes diabetic retinopathy, microangiopathy, renal failure or Alzheimer's disease.

18. The method according to clause 16, where the inflammatory reaction is caused by a glycated protein or the accumulation of end products of deep glycation.

19. The method of claim 18, wherein the glycated protein or the accumulation of end products of deep glycation is mediated by a pro-inflammatory cytokine.

20. The method according to claim 19, where the pro-inflammatory cytokine includes IL-6, IL-1, TMF-a or MCP-1.

21. The method according to clause 16, where the proliferation of smooth muscle cells is inhibited by inducing expression of perlecan.

22. The method according to clause 16, where the proliferation of smooth muscle cells is mediated by a pro-inflammatory cytokine.

23. The method of claim 22, wherein the pro-inflammatory cytokine comprises IL-6, IL-1, TNF-a, or MCP-1.

24. A method of treating or preventing an undesirable inflammation in a human or animal, comprising administering to a human or animal with an undesirable inflammation a composition comprising a therapeutically or prophylactically effective amount of a compound according to claim 1.

25. A method of treating or preventing undesirable proliferation of smooth muscle cells in a human or animal, comprising administering to a human or animal with undesirable proliferation of smooth muscle cells a composition comprising a therapeutically or prophylactically effective amount of a compound according to claim 1.

26. A method of treating or preventing a disease or disorder mediated by a cell adhesion molecule, comprising administering to a patient in need thereof a composition comprising a therapeutically or prophylactically effective amount of a compound according to claim 1.

27. The method of claim 26, wherein the disease or disorder mediated by cell adhesion molecules is an inflammatory disorder or cardiovascular disease.

28. The method of claim 27, wherein the inflammatory disorder is rheumatoid arthritis, osteoarthritis, asthma, dermatitis, psoriasis, organ transplantation or allograft rejection, autoimmune diabetes, or multiple sclerosis.

29. The method of claim 27, wherein the cardiovascular disease is atherosclerosis, restenosis, coronary artery disease, angina pectoris, dyslipidemia, small artery disease, diabetes mellitus, diabetic nephropathy, or diabetic retinopathy.

30. The method according to p, where the cell adhesion molecule is VCAM-1.

31. The method of claim 26, further comprising administering a therapeutically or prophylactically effective amount of at least one other drug, including a platelet aggregation inhibitor, an antithrombotic agent, calcium channel blocker, an angiotensin converting enzyme inhibitor, a β-blocker, a non-steroidal anti-inflammatory agent, a COX inhibitor II, corticosteroid, TNF-a modulating agent, HMGCoA reductase inhibitor, PPAR-β agonist, high-density lipoprotein elevator (HDL elevator) or reti OID.

32. The method according to p, where at least one other drug is aspirin, diltazem, nephidipine, captopril, enalopril, propanalol, ibuprofen, indomethacin, sulindac, rofecoxib, celesoxib, etanercept or infliximab.

33. A method for treating or preventing cancer in a human or animal, comprising administering to a human or animal a composition comprising a therapeutically or prophylactically effective amount of a compound according to claim 1.

34. The method of claim 33, wherein the cancer includes melanoma, prostate cancer, leukemia, lymphoma, non-small cell lung cancer, central nervous system cancer, breast cancer, colon cancer, ovarian cancer, or kidney cancer.

35. A method of inhibiting the proliferation of smooth muscle cells in a human or animal, comprising administering to a human or animal a composition comprising a therapeutically or prophylactically effective amount of a compound according to claim 1.

36. A method of inhibiting the inflammatory response of human or animal endothelial cells, comprising administering to a human or animal a composition comprising a therapeutically or prophylactically effective amount of a compound according to claim 1.

37. A method of treating or preventing vasculopathy of an organ transplant in a human or animal, comprising administering to a human or animal a composition comprising a therapeutically or prophylactically effective amount of a compound according to claim 1.

38. The method according to clause 37, where the organ is a liver, kidney, heart, lungs, pancreas, pancreatic islet and skin.

39. The method according to clause 37, further comprising administering a therapeutically or prophylactically effective amount of an immunosuppressive agent.

40. The method according to § 39, where the immunosuppressive agent is CellCept, Gengraf, Micrhogam, Neoral, Orthoclone OKT3, Prograf, Rapamune, Sandimmune, Thymoglobulin, Zenapax.

41. The method according to § 39, where the introduction is oral, parenteral, subcutaneous, intramuscular, intravenous, intraarticular, intracapsular, intracranial, intracavitary, intracranial, intracranial, intracranial, intracranially, , intrapelvic, intrapericardial, intraperitoneal, intrapleural, intraprostatic, intrapulmonary, intrarectal, intrarenal, intra retinal, intraspinal, intrasinovial, intrathoracic, intrauterine, intravesical, bolus, vaginal, rectal, buccal, sublingual, intranasal or transdermal.

42. The method according to § 39, where the immunosuppressive agent is administered before the composition.

43. The method according to § 39, where the immunosuppressive agent is administered after the composition.

44. The method according to § 39, where the immunosuppressive agent is administered simultaneously with the composition.

45. A method for the treatment or prevention of restenosis in a human or animal, comprising administering to a human or animal a composition comprising a therapeutically or prophylactically effective amount of a compound according to claim 1.

46. A method for treating or preventing atherosclerosis in a human or animal, comprising administering to a human or animal a composition comprising a therapeutically or prophylactically effective amount of a compound according to claim 1.

47. A method of treating an illness mediated by inflammation in a human or animal, comprising administering to a human or animal a composition comprising a therapeutically or prophylactically effective amount of a compound according to claim 1.

48. The method of claim 47, wherein the disease mediated by inflammation is an autoimmune disease.

49. The method of claim 48, wherein the autoimmune disease is focal alopecia, ankylosing spondylitis, antiphospholipid syndrome, autoimmune Addison’s disease, autoimmune hemolytic anemia, autoimmune hepatitis, Behcet’s disease, pulmonary carcinoma disease, dermatomephiosis, pemphioma pulmonary disease, immune dysfunction (CFIDS), chronic inflammatory demyelinating polyneuropathy, granulomatous allergic angiitis, cicatricial pemphigoid, CREST syndrome, pain knowledge of cold agglutinin, Crohn’s disease, lupus erythematosus, essential mixed cryoglobulinemia, fibromyalgia-fibromyositis, Graves disease, Guillain-Barre disease, Hashimoto's thyroiditis, idiopathic idiopathic thrombocytosis, idiopathic thrombocytopenia, thrombocytopenia, thrombocytopenia, and idiopathic thrombocytopenia lichen planus, Meniere's disease, mixed connective tissue disease, multiple sclerosis, asthenic bulbar palsy, pemphigus vulgaris, malignant anemia, nodular polyarteritis, polychondria, pluriglandular syndromes, polymyalgia rheumatism, polymyositis and dermatomyositis, primary agammaglobulinemia, primary biliary cirrhosis, psoriasis, vibro disease, human rheumatoid rheumatoid syndrome, rheumatoid fever, lupus erythematosus, Takayasu syndrome, temporal arteritis / giant cell arteritis, ulcerative colitis, uveitis, vasculitis, Viti yoke or Wegener's granulomatosis.

50. A method of treating or preventing metastases in a human or animal, comprising administering to a human or animal a composition comprising a therapeutically or prophylactically effective amount of a compound according to claim 1.

51. A method of modulating perlecan activity in a human or animal, comprising administering to a human or animal a composition comprising a therapeutically effective amount of a compound according to claim 1.

52. A method for modulating heparanase in a human or animal, comprising administering to a human or animal a composition comprising a therapeutically effective amount of a compound according to claim 1.

53. A stent coated with a composition comprising a compound according to claim 1.

54. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, diluent, excipient or solvate.

55. The pharmaceutical composition according to item 54 in the form of tablets, capsules, powder, syrup, solution, suspension.

56. A medical device coated with a composition comprising a compound according to claim 1.

57. The medical device according to claim 56, wherein the medical device means a shunt, a device for connecting a colostomy receiver, an ear drainage tube, a pacemaker wire and an implantable defibrillator, suture material, a brace, an anastomosis device, a spinal disc, a bone nail, a suture attachment device, a hemostatic barrier, clamp, screw, plate, staple bracket, vascular implant, tissue adhesive or sealant, tissue skeleton, bone substitute, intraluminal device and vascular support.

58. A method for treating or preventing cardiovascular disease in a human or animal, comprising administering to a human or animal a composition comprising a therapeutically effective amount of a compound according to claim 1.

59. The method of claim 58, wherein the cardiovascular disease is atherosclerosis, restenosis, coronary artery disease, angina pectoris, dyslipidemia, small artery disease, diabetes mellitus, diabetic nephropathy, or diabetic retinopathy.